连朴饮加减方对幽门螺杆菌相关性胃炎小鼠胆汁酸代谢的影响研究  

Effect of Modified Lianpo Decoction on Bile Acid Metabolism in Helicobacter pylori-associated Gastritis Mice

作　　者：丁辛 吕文亮[2] 张思依 张平[2] 周姝含 刘之义 毛宁峰 刘雪峰 DING Xin;LYU Wenliang;ZHANG Siyi;ZHANG Ping;ZHOU Shuhan;LIU Zhiyi;MAO Ningfeng;LIU Xuefeng(Pharmacy Faculty,Hubei University of Chinese Medicine,Wuhan 430065,China;School of Traditional Chinese Medicine,Hubei University of Chinese Medicine,Wuhan 430061,China)

机构地区：[1]湖北中医药大学药学院,武汉430065 [2]湖北中医药大学中医学院,武汉430061

出　　处：《世界中医药》2025年第2期223-230,238,共9页World Chinese Medicine

基　　金：国家自然科学基金青年科学基金项目(82204898)——TRIM31调控NLRP3炎症小体参与幽门螺杆菌导致胃黏膜损伤的分子机制及连朴饮加味方的干预作用;湖北中医药大学青苗计划项目(2022ZZXQ023)——连朴饮加减方主要化学成分在体内外影响球形变幽门螺杆菌的分子机制研究;湖北省2022年度博士后创新研究岗位资助项目——连朴饮加减方主要化学成分在体内外影响球形变幽门螺杆菌的分子机制研究;湖北省自然科学基金创新发展联合基金项目(2024AFD293)——基于膜原理论口腔幽门螺杆菌透膜入里致胃黏膜损伤的分子机制及达原饮干预影响;湖北中医药大学“双一流”建设重点类专项科研项目(2023ZZXJB003)——慢性胃炎脾胃湿热证生物学基础研究及方证效应验证。

摘　　要：目的:研究连朴饮加减方对克拉霉素耐药幽门螺杆菌相关性胃炎(HAG)小鼠胆汁酸的影响。方法:将50只Balb/c小鼠分为5组:生理盐水组、病理模型组、连朴饮加减方组、抗生素四联组、联合观察组。以0.3 mL药物连续干预14 d,生理盐水组和病理模型组给予生理盐水,连朴饮加减方组给予0.5 g/mL连朴饮加减方;抗生素四联组给予四联药物的生理盐水溶液;联合观察组给予含有四联药物的连朴饮加减方溶液。干预后以胃黏膜Warthin-Starry银染色观察上皮细胞形态;酶联免疫吸附试验(ELISA)测定肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)水平;以液相色谱质谱联用技术定量胆囊胆汁酸。结果:连朴饮加减方治疗后胃黏膜上皮细胞结构相对清晰完整,腺体排列较为均匀整齐,可预防球形变耐药现象。与病理模型组比较,连朴饮加减方组TNF-α水平降低(P<0.05)。与生理盐水组比较,抗生素四联组有牛磺鹅去氧胆酸(TCDCA)、牛磺脱氧胆酸(TDCA)、牛磺猪去氧胆酸(THDCA)、牛磺石胆酸(TLCA)、甘氨熊脱氧胆酸(GUDCA)共5种胆汁酸差异有统计学意义(P<0.05),连朴饮加减方组仅有THDCA。结论:连朴饮加减方在小鼠体内可降低TNF-α水平,减轻炎症反应;与四联疗法比较,在维持胆汁酸生理稳态上具有优势,TLCA、GUDCA可作为药效的判别指标。Objective:To study the effect of modified Lianpo Decoction on bile acids in mice with clarithromycin-resistant Helicobacter pylori-associated gastritis(HAG).Methods:Fifty Balb/c mice were randomly divided into five groups:saline group,pathological model group,modified Lianpo Decoction group,antibiotic quadruple therapy group,and combination therapy group.The groups were continuously treated with 0.3 mL of the respective solution for 14 days.The saline group and pathological model group were given saline,the modified Lianpo Decoction group was given modified Lianpo Decoction at 0.5 g/mL,the antibiotic quadruple therapy group was given a saline solution of the quadruple antibiotics,and the combination therapy group was given a solution containing both the quadruple antibiotics and the modified Lianpo Decoction.After the intervention,Warthin-Starry silver staining was used to observe the epithelial cell morphology of the gastric mucosa.Enzyme-linked immunosorbent assay(ELISA)was performed to measure tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)levels.Liquid chromatography-mass spectrometry(LC-MS)was used to quantify bile acids in the gallbladder.Results:After treatment with modified Lianpo Decoction,the gastric mucosal epithelial cell structure was relatively clear and intact,and the glandular arrangement was more uniform and orderly,which could prevent spherical shape and drug resistance.Compared with the pathological model group,the TNF-αlevel in the modified Lianpo Decoction group was significantly reduced(P<0.05).Compared with the saline group,the antibiotic quadruple therapy group showed significant differences in five bile acids:taurine glycochenodeoxycholic acid(TCDCA),taurine deoxycholic acid(TDCA),taurine hyodeoxycholic acid(THDCA),taurine lithocholic acid(TLCA),and glycocholic acid(GUDCA)(P<0.05),while only THDCA showed a significant difference in the modified Lianpo Decoction group.Conclusion:Modified Lianpo Decoction can reduce TNF-αlevels and alleviate inflammation in mice.Compared with quad

关 键 词：连朴饮 克拉霉素耐药 幽门螺杆菌 胃炎 胆汁酸 代谢组学 幽门螺杆菌 球形变 炎症介质 

分 类 号：R285.5[医药卫生—中药学] R256.3[医药卫生—中医学]